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Quantitative Assay Measures Low Levels of HER2 with Renewed Accuracy

May 20, 2022

Researchers at Yale Cancer Center have developed a new quantitative assay to measure the amount of HER2 protein in patients with breast cancer with increased accuracy. The improved data may provide new options for treatment for patients previously found ineligible for treatment based on traditional HER2 screening assays. The findings were published today in Laboratory Investigation.

Patients with breast cancer are tested for expression of human epidermal growth factor receptor 2 (HER2) protein. If the testing assay is scored 2+ or 3+, the patient is considered HER2 ‘positive’ and is eligible for anti-HER2 therapy. The historic FDA approved HER2-targeted therapies, including trastuzumab, pertuzumab, and lapatinib, which have significantly improved outcomes for HER2+ patients but these drugs are not useful for patients who score 0 or 1+ on the current assay. Recent data describes another HER2-targeted therapy, Trastzumab deruxtecan, that is effective in patients with low levels of HER2. This new assay will be helpful in identifying those patients for treatment.

The Yale team developed a new diagnostic assay based on mass spectrometry and using the AQUA™ method of quantitative immunofluorescence to accurately detect and measure lower levels of HER2 and return the data as amol/mm2. Using the quantitative assay, the team determined that low HER2 range expression is between 2 and 20 attomol/mm2. Following review of 364 breast cancer cases at Yale Cancer Center, 67% of the samples were found to have HER2 expression in the range where patients may respond to Trastzumab deruxtecan.

“Our research shows that patients that are scored a 0 or 1+ through traditional assays may have enough target to benefit from the newest anti-HER2 treatment,” said David Rimm, MD, PhD, Anthony N. Brady Professor of Pathology and Professor of Medicine (Medical Oncology), Director of Yale Pathology Tissue Services, and senior author on the paper. “As more targeted therapies become available for patients, the need for accurate data is crucial to ensure each patient can access the right treatment.”

As more targeted therapies become available for patients, the need for accurate data is crucial to ensure each patient can access the right treatment.

Dr. David Rimm

Funding for the study was supported by InviCRO/Konica/Minolta, the Breast Cancer Research Foundation, and Yale Cancer Center.

The following Yale authors contributed to this study: Myrto Moutafi, Charles J. Robbins, Vesal Yaghoobi, Aileen I. Fernandez, Sandra Martinez-Morilla, Vasiliki Xirou, Yalai Bai, Yan Song, and Patricia Gaule.

Submitted by Renee Gaudette on May 20, 2022